177Lu-PSMA-617 vs. Androgen Receptor-directed Therapy in the Treatment of Progressive Metastatic Castrate Resistant Prostate Cancer

PSMAfore: A Phase III, Open-label, Multi-Center, Randomized Study Comparing 177Lu-PSMA-617 vs. a Change of Androgen Receptor-directed Therapy in the Treatment of Taxane Naïve Men With Progressive Metastatic Castrate Resistant Prostate Cancer

ClinicalTrials.gov Identifier: NCT04689828

Novartis Reference Number: CAAA617B12302

Last Update: Nov 10, 2021

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All compounds are either investigational or being studied for (a) new use(s). Efficacy and safety have not been established. There is no guarantee that they will become commercially available for the use(s) under investigation. 

Study Description

The purpose of this study is to determine whether 177Lu-PSMA-617 improves the rPFS or death compared to a change in ARDT in mCRPC participants that were previously treated with an alternate ARDT and not exposed to a taxane-containing regimen in the CRPC or mHSPC settings.

Approximately 450 participants will be randomized (225 per treatment group).

Condition 
Prostatic Neoplasms
Phase 
Phase 3
Overall status 
Recruiting
Enrollment count 
450 participants
Start date 
Jun 15, 2021
Completion date 
Apr 27, 2023
Gender 
Male
Age(s)
18 Years and older (Adult, Older Adult)

Interventions

Radiation
177Lu-PSMA-617
administered intravenously once every 6 weeks (1 cycle) for 6 cycles
Radiation
68Ga-PSMA-11
single intravenous dose of approximately 150 MBq. Administered dose must not be lower than 111 MBq or higher than 185 MBq (3 - 5 mCi).
Drug
ARDT
administered orally on a continuous basis, as per package insert and guidelines
Other
Best supportive care
Best supportive/best standard of care as defined by the local investigator

Eligibility Criteria

Inclusion Criteria:

Participants eligible for inclusion in this study must meet all of the following criteria:

Signed informed consent must be obtained prior to participation in the study
Participants must be adults ≥ 18 years of age
Participants must have an ECOG performance status of 0 to 1
Participants must have histological pathological, and/or cytological confirmation of adenocarcinoma of the prostate
Participants must be 68Ga-PSMA-11 PET/CT scan positive, and eligible as determined by the sponsor's central reader
Participants must have a castrate level of serum/plasma testosterone (< 50 ng/dL or < 1.7 nmol/L)
Participants must have received one prior approved ARDT (for example, abiraterone, enzalutamide, darolutamide, or apalutamide, etc.) and have documented progression on therapy

Participants must have progressive mCRPC. Documented progressive mCRPC will be based on at least 1 of the following criteria:

Serum/plasma PSA progression defined as 2 consecutive increases in PSA over a previous reference value measured at least 1 week prior. The minimal start value is 2.0 ng/mL
Soft-tissue progression defined [PCWG3-modified RECIST v1.1 (Eisenhauer et al 2009, Scher et al 2016)]
Progression of bone disease: evaluable disease or one or more new bone lesions(s) by bone scan (PCWG3 criteria (Scher et al 2016))
Participants must have ≥ 1 metastatic lesion that is present on screening/baseline CT, MRI, or bone scan imaging obtained ≤ 28 days prior to beginning study therapy
Participants must have recovered to ≤ Grade 2 from all clinically significant toxicities related to prior therapies (i.e. prior chemotherapy, radiation, etc.) except alopecia

Participants must have adequate organ function:

Bone marrow reserve:
ANC ≥ 1.5 x 109/L
Platelets ≥100 x 109/L
Hemoglobin ≥ 9 g/dL
Hepatic:
Total bilirubin < 2 x the institutional upper limit of normal (ULN). For participants with known Gilbert's Syndrome ≤ 3 x ULN is permitted
ALT or AST ≤ 3.0 x ULN OR ≤ 5.0 x ULN for participants with liver metastases
Renal:
eGFR ≥ 50 mL/min/1.73m2 using the Modification of Diet in Renal Disease (MDRD) equation
Albumin ≥ 2.5 g/dL
Candidates for change in ARDT as assessed by the treating physician

Exclusion Criteria:

Participants meeting any of the following criteria are not eligible for inclusion in this study:

Previous treatment with any of the following within 6 months of randomization: Strontium-89, Samarium-153, Rhenium-186, Rhenium-188, Radium-223, hemi-body irradiation
Previous PSMA-targeted radioligand therapy
Prior treatment with cytotoxic chemotherapy for castration resistant or castrate sensitive prostate cancer (e.g., taxanes, platinum, estramustine, vincristine, methotrexate, etc.), immunotherapy or biological therapy [including monoclonal antibodies]) [Note: Taxane exposure (maximum 6 cycles) in the adjuvant or neoadjuvant setting is allowed if 12 months have elapsed since completion of this adjuvant or neoadjuvant therapy]
Any investigational agents within 28 days prior to day of randomization
Known hypersensitivity to any of the study treatments or its excipients or to drugs of similar classes
Other concurrent cytotoxic chemotherapy, immunotherapy, radioligand therapy, or investigational therapy
Transfusion or use of bone marrow stimulating agents for the sole purpose of making a participant eligible for study inclusion
Patients with a history of CNS metastases that are neurologically unstable, symptomatic, or receiving corticosteroids for the purpose of maintaining neurologic integrity. Participants with CNS metastases are eligible if received therapy (surgery, radiotherapy, gamma knife), asymptomatic and neurologically stable without corticosteroids. Participants with epidural disease, canal disease and prior cord involvement are eligible if those areas have been treated, are stable, and not neurologically impaired.
Symptomatic cord compression, or clinical or radiologic findings indicative of impending cord compression

History or current diagnosis of the following ECG abnormalities indicating significant risk of safety for study participants:

Concomitant clinically significant cardiac arrhythmias, e.g. sustained ventricular tachycardia, complete left bundle branch block, high-grade AV block (e.g., bifascicular block, Mobitz type II and third degree AV block)
History of familial long QT syndrome or known family history of Torsades de Pointe
Cardiac or cardiac repolarization abnormality, including any of the following: History of myocardial infarction (MI), angina pectoris, or CABG within 6 months prior to starting study treatment

Concurrent serious (as determined by the Principal Investigator) medical conditions, including, but not limited to New York Heart Association class III or IV congestive heart failure, history of congenital prolonged QT syndrome, uncontrolled infection, known active hepatitis B or C or other significant co-morbid conditions that in the opinion of the investigator would impair study participation or cooperation

HIV-infected participants who are at a low risk of AIDS-related outcomes may participate in this trial.
Participants with an active documented COVID-19 infection (any grade of disease severity) at time of informed consent may be included only when completely recovered (in accordance with local guidance) and had no symptoms for at least 28 days before the first dose of study medication.
Diagnosed with other malignancies that are expected to alter life expectancy or may interfere with disease assessment. Participants with a prior history of malignancy that has been adequately treated and who have been disease free for more than 3 years are eligible, as are participants with adequately treated non-melanoma skin cancer, superficial bladder cancer
Sexually active males unwilling to use a condom during intercourse while taking study treatment and for 6 months after stopping study treatment. A condom is required for all sexually active male participants to prevent them from fathering a child AND to prevent delivery of study treatment via seminal fluid to their partner. In addition, male participants must not donate sperm for the time period specified above. If local regulations deviate from the contraception methods listed above to prevent pregnancy, local regulations apply and will be described in the ICF
Concurrent bladder outflow obstruction or unmanageable urinary incontinence
History of somatic or psychiatric disease/condition that may interfere with the objectives and assessments of the study
Any condition that precludes raised arms position
Presence of any mutations or biomarkers that are known as predictors of better response to treatments other than ARDT (e.g., AR-V7 or BRCA) as assessed by the investigator
Not able to understand and to comply with study instructions and requirements

Study Locations

United States
Tulane University Health Sciences Center
Recruiting
New Orleans, 70112
Louisiana
United States
Dana-Farber Cancer Institute Dana-Farber Cancer Institute_
Recruiting
Boston, 02115
Massachusetts
United States
Urology Cancer Center PC
Recruiting
Omaha, 68130
Nebraska
United States
Nebraska Cancer Specialists Oncology Hematology West
Recruiting
Omaha, 68154
Nebraska
United States
Seattle Cancer Care Alliance
Recruiting
Seattle, 98105
Washington
United States
Austria
Novartis Investigative Site
Recruiting
Innsbruck, 6020
Tyrol
Austria
Novartis Investigative Site
Recruiting
Linz, A-4010
-
Austria
Novartis Investigative Site
Recruiting
Wien, 1090
-
Austria
Czech Republic
Novartis Investigative Site
Recruiting
Olomouc, 775 20
CZE
Czech Republic
France
Novartis Investigative Site
Recruiting
Angers cedex 02, 49055
-
France
Novartis Investigative Site
Recruiting
Bordeaux, 33076
-
France
Novartis Investigative Site
Recruiting
Clermont-Ferrand, 63011
-
France
Novartis Investigative Site
Recruiting
Lyon Cedex, 69373
-
France
Novartis Investigative Site
Recruiting
Paris, 75970
-
France
Novartis Investigative Site
Recruiting
Villejuif Cedex, 94800
-
France
Netherlands
Novartis Investigative Site
Recruiting
Nijmegen, 6525 GA
Netherland
Netherlands
Slovakia
Novartis Investigative Site
Recruiting
Bratislava, 83310
Slovak Republic
Slovakia
Spain
Novartis Investigative Site
Recruiting
Malaga, 29010
Andalucia
Spain
Novartis Investigative Site
Recruiting
Sevilla, 41013
Andalucia
Spain
Novartis Investigative Site
Recruiting
Barcelona, 08035
Catalunya
Spain
Novartis Investigative Site
Recruiting
Barcelona, 08036
Catalunya
Spain
Novartis Investigative Site
Recruiting
Hospitalet de LLobregat, 08907
Catalunya
Spain
Novartis Investigative Site
Recruiting
Valencia, 46009
Comunidad Valenciana
Spain
Novartis Investigative Site
Recruiting
Santiago de Compostela, 15706
Galicia
Spain
Novartis Investigative Site
Recruiting
El Palmar, 30120
Murcia
Spain
Novartis Investigative Site
Recruiting
Barcelona, 08041
-
Spain
Novartis Investigative Site
Recruiting
Madrid, 28009
-
Spain
Novartis Investigative Site
Recruiting
Madrid, 28040
-
Spain
Novartis Investigative Site
Recruiting
Madrid, 28041
-
Spain
Novartis Investigative Site
Recruiting
Madrid, 28222
-
Spain
Novartis Investigative Site
Recruiting
Valencia, 46026
-
Spain
Sweden
Novartis Investigative Site
Recruiting
Goteborg, 413 45
-
Sweden
Novartis Investigative Site
Recruiting
Lund, 221 85
-
Sweden
Novartis Investigative Site
Recruiting
Stockholm, 17176
-
Sweden
United Kingdom
Novartis Investigative Site
Recruiting
Sutton, SM2 5PT
Surrey
United Kingdom

Contacts

Name: 
Novartis Pharmaceuticals
Phone: 
Name: 
Novartis Pharmaceuticals
Phone: 

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Call 1-888-669-6682 or email [email protected]